Discovering a new paradigm: Gut microbiota as a central modulator of sexual health

Table 1 Short-chain fatty acids: Composition, absorption, and circulatory levels

Short-chain fatty acid	Relative abundance (%)	Fecal concentration (g/kg)	Main absorption route	Plasma concentration (μM)	Biological function
Acetate	About 60%	About 60 g/kg	Absorbed via MCTs in the colon; partially crosses the BBB	100-200	Primary energy source for peripheral tissues, precursor for lipogenesis, contributes to appetite regulation and gut-brain communication
Propionate	About 20%	About 10-20 g/kg	Mainly used by hepatocytes, with a small fraction entering the circulation	1-15	Plays a crucial role in hepatic gluconeogenesis and cholesterol metabolism, modulates inflammatory pathways
Butyrate	About 20%	About 3.5-32.6 g/kg	Primary energy source for colonocytes; also crosses the BBB	1-15	Essential for maintaining gut barrier integrity, possesses anti-inflammatory and neuroprotective properties

MCTs: Monocarboxylate transporters; BBB: Blood-brain barrier.

Table 2 Impact of gut microbiota on inflammation and sexual health

Microbiota factor	Effect on inflammation	Pathways and mechanisms	Impact on sexual health
SCFA production	Reduces pro-inflammatory cytokines (IL-6, TNF-α) and enhances anti-inflammatory responses (IL-10)	Activates GPCRs, inhibits NF-κB signaling, enhances Treg activity	Modulates neurotransmitter levels, improving libido and mood stability
Gut barrier integrity	Strengthens intestinal epithelium, reducing systemic endotoxin levels	Increases tight junction proteins (occludin, claudin), reduces LPS translocation	Prevents inflammatory-induced sexual dysfunction (e.g., erectile dysfunction); Improved gut integrity supports neurotransmitter balance, positively affecting sexual desire and pleasure
Dysbiosis (microbial imbalance)	Promotes endotoxemia, activates TLR4 signaling, increases systemic inflammation	Activates TLR4, increases pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), disrupts HPA axis function	Neuroinflammation disrupts dopamine and serotonin homeostasis, potentially reducing libido and motivation; Contributes to decreased libido, erectile dysfunction, and hormonal imbalances
Neurotransmitter synthesis	Modulates 5-HT, DA, NE, Ach and GABA production, impacting brain function	Regulates tryptophan metabolism, modulates serotonin biosynthesis via gut-derived 5-HT; NO and PGs influence DA, 5-HT, NE, and ACh release in key brain regions	Reduced serotonin synthesis may lead to mood instability and decreased sexual interest; Altered neurotransmitter release may impair arousal, orgasm, and emotional connection; Influences arousal, mood, and stress-related sexual disorders

SCFA: Short-chain fatty acid; IL: Interleukine; TNF-α: Tumor necrosis factor α; GPCRs: G-protein coupled receptors; NF-κB: Nuclear factor kappa B; TLR4: Toll-like receptor 4; HPA: Hypothalamic-pituitary-adrenal; 5-HT: Serotonine; DA: Dopamine; NE: Norepinephrine; Ach: Acetylcholine; NO: Nitric oxide; PGs: Prostaglandins; LPS: Lipopolysaccharide; Treg: Regulatory T cell; GABA: Gamma-aminobutyric acid.